The impact of daily sodium intake on posttransplant hypertension in kidney allograft recipients

INTRODUCTION: Posttransplant hypertension is a well-known risk factor for long-term allograft failure and mortality in kidney recipients. Although dietary sodium restriction is a widely recommended nonpharmacological measure for control of blood pressure (BP), no detailed investigation has been conducted regarding the impact of dietary sodium restriction on this condition. METHODS: Thirty-two patients on antihypertensive treatment completed the study. They were randomly divided into two groups: controls (group 1) versus strict sodium diet (group 2; 80 to 100 mmol sodium daily). After randomization, 24-hour urine for sodium measurement, BP, and allograft functions were recorded at baseline and after 3 months. BP treatment was reevaluated at each visit throughout the study. RESULTS: At baseline, there was no significant difference in age, sex, serum creatinine, systolic and diastolic BP, antihypertensive drugs, or 24-hour urinary sodium levels between the groups. After 3 months, daily urinary sodium excretion (from 190+/-75 to 106+/-48 mEq/d, P<.0001), systolic BP (from 146+/-21 to 116+/-11 mm Hg), and diastolic BP (from 89+/-8 to 72+/-10 mm Hg) had significantly decreased in group 2, while no significant changes were observed in group 1. CONCLUSION: Low sodium intake in combination with antihypertensive treatment appears to efficiently control BP in kidney allograft recipients with hypertension. Twenty-four-hour urinary sodium excretion should be checked regularly in these patients as a useful marker to indicate whether the patient complies with low sodium intake.     

Association between granzyme B and perforin I polymorphisms and allograft outcomes in Hispanic kidney transplant recipients

Granzyme B (GZMB) and perforin 1 gene (PRF1) are key effector molecules of cytotoxic T lymphocytes, in causing acute and chronic solid organ transplant rejection. In this study, we analyzed the impact of GZMB and PRF1 polymorphism on kidney allograft outcomes. In all, 527 de novo kidney Hispanic allograft recipients were genotyped for PRF1 (rs10999426, rs35947132) and GZMB (rs8192917, rs7144366). PRF1 (rs10999426, rs35947132) G alleles and GG genotypes were negatively associated with allograft rejection, demonstrating protection against allograft rejection (OR = 0.61, p = 0.005 for rs1099946; OR = 0.4, p = 0.01 for rs 35947132). On the other hand, the GA heterozygosity of PRF1 was found marginally associated with the rejection group (OR = 1.53, p = 0.05 for rs10999426; OR = 2.24, p = 0.07 for rs35947132). There was a significant increase in allograft survival in time period studied for the PRF1 (rs10999426) GG genotype, while the GA heterozygosity was associated with graft failure. We found no association for polymorphic markers in GZMB gene with allograft rejection. Survival was significantly improved for patients who were homozygous TT for the GZMB (rs8192917) (TT vs. CC/TT, p = 0.041). The result suggests that PRF1 and GZMB gene polymorphisms may determine the incidence of acute rejection or graft survival among Hispanic allograft recipients.     

Pneumonia in kidney allograft recipients

Infectious complications, including pneumonia, remain one of the leading causes of morbidity and mortality in kidney allograft recipients. The aim of the study was to evaluate the relationship between pneumonia occurrence and treatment duration and recipient age, cause of native kidney insufficiency, dialysis duration, time between transplantation and onset, HLA matching, PRA immunosuppressive protocol, acute rejection incidence and treatment, kidney function at the pneumonia onset, as well as presence of comorbid conditions. One hundred and twenty pneumonia cases occurred in kidney allograft recipients transplanted between 1991 and 2000 with 12 to 120 months follow-up. Twenty five percentage of pneumonia episodes were diagnosed during the first posttransplant month, 25% between 2 and 6 months, and 25% at 0.5 to 3 years. Treatment duration measured from pneumonia onset to the study endpoint of recovery, which was defined as antibiotic withdrawal, show 50% of patient we cured after 15 days and 75% after 24 days of treatment. The risk of prolonged pneumonia treatment was associated with: second versus first kidney transplantation with RR = 2.3 (P <.02) and medians of treated time 28 versus 15 days; as well as serum creatinine level above 2 mg/dL (RR = 1.4; P <.098). Exposure to enhanced-potency immunosuppressive protocols including induction therapy with mono- or polyclonal antibodies increased the RR = 1.65 (P <.02), and lengthened the time to 18 versus 14 days. Maintenance immunosuppression with agents other than cyclosporine also enhanced the risk. (RR = 2.18; P <.068).     

Association of treatment with 15-deoxyspergualin and BK virus nephropathy in kidney allograft recipients

OBJECTIVE: BK virus nephropathy (BKVN) has been proposed as an important cause of allograft dysfunction and loss in kidney allograft recipient over the last decade. Intense immunosuppression and tubular injury have been shown to promote the replication of polyomavirus. 15-deoxyspergualin (DSG), an effective immunosuppressive agent, is used as a rescue drug for acute rejection in clinical renal transplantation in Japan. To determine whether DSG is a risk factor for BKVN and outline the relationship among BKVN, DSG, and other risk factors, we analyzed 88 patients who received living-related renal transplantation between January 1999 and April 2003. METHODS: A total of 114 biopsy specimens from 88 living-related kidney transplantation recipients (performed between January 1999 to April 2003) were retrospectively analyzed. Patients received immunosuppression therapy based on calcineurin inhibitors and corticosteroid [tacrolimus (TAC) 33 and cyclosporin (CyA) 55]. Additionally, mycophenolate mofeteil (MMF) was used in 21 patients; DSG was used in seven patients; and anti-CD3 monoclonal antibody was used in 16 patients. We analyzed the degree of donor/recipient human leucocyte antigen (HLA) compatibility assessed by the number of HLA-A, -B, and -DR-mismatched antigens in 88 patients. The diagnosis of BKVN was made by the light microscopic examination and a positive immunohistochemical staining of anti-40 antibody in biopsy specimens. Patients were divided into two groups of group A (mild histological change) and group B (moderate or severe histological change) to determine the risk factors in different histological staging. The clinical course of two typical patients in different histological stage is described briefly to outline the risk factors of BKVN. RESULTS: We identified seven cases of BKVN (8.0%) from 88 transplanted patients. Significantly higher incidence of combination regimen consisting of TAC and MMF in BKVN group was noticed compared with non-BKVN group (57.1% vs. 9.9%; p = 0.003). BKVN was associated with a significantly higher incidence of DSG administration compared with non-BKVN group (57.1% vs. 3.7%; p 相似文献   

mTOR inhibitor-associated proteinuria in kidney transplant recipients

The use of mammalian target of rapamycin inhibitor (mTOR-I) after kidney transplantation has been associated with a higher incidence of proteinuria compared with calcineurin inhibitors (CNIs). This review will focus on mTOR-I-associated proteinuria in different settings after kidney transplantation: de novo mTOR-I treatment in combination with CNI, de novo mTOR-I-containing and CNI-free treatment, early conversion from a CNI-based regimen to an mTOR-I-based regimen, and late conversion. Some possible mechanisms of mTOR-I-induced proteinuria will also be reviewed.     

Compliance with lifestyle recommendations in kidney allograft recipients

Background

Many factors affect long-term graft and patient survival. Compliance with lifestyle recommendation may be an important factor. Lifestyle modifications may play a therapeutic and protective role against graft failure and possible death.

Methods

The aim of this work was to assess compliance with lifestyle recommendations among 110 kidney allograft recipients. All patients were asked to complete a questionnaire regarding life style, frequency of outpatient visits, self-control, diet, physical activity and addictions.

Results

The mean age of the population was 48.79 ± 13.18 years, and their mean time after transplantation was 69 ± 44.5 years with a mean serum creatinine value of 1.45 ± 0.7 mg/dL. Physicians were the major source of information (40%) for patients while in the hospital; nurses informed patients in only 5.5% of cases. The majority of patients (97.5%) attended regular outpatient clinic visits. A similar percentage of subjects regularly measured their blood pressure at home. One-fifth of the patient wrote a self-control diary. Only 55.5% of patients knew the immunosuppressive regimen, including the doses of the medications. An overweight condition was diagnosed in 39%, with obesity in 22%; 16% of the patients were smokers; one-fourth of the patients drank alcohol at least several times a month; 85.3% of patients did not change their diet after kidney transplantation; and one-half of the patients (64.2%) were not aware of dietary recommendations after kidney transplantation.

Conclusions

The majority of patients regularly attended the outpatient clinic and ingested immunosuppressive medications. However, their knowledge regarding diet, cancer prophylaxis, and self-control was insufficient. Therefore, there is a need to introduce more intense organizational and educational activities to improve patient knowledge.     

Clinical significance of proteinuria at posttransplant year 1 in kidney transplantation

Purpose

Proteinuria in the nontransplant population is a progressive renal disease. We analyzed the prevalence and clinical significance of proteinuria as well as factors related to its degree at posttransplant year 1 among kidney transplant recipients.

Methods

We measured protein in a 24-hour urine among 644 recipients from January 1996 to December 2010.

Results

Among 372 male and 272 female recipients, the mean amount of urinary protein was 424.4 ± 1010 mg/d (range, 13.88-8691) including 388 (60.2%) subjects with microproteinuria and the other 256 (39.8%) with overt proteinuria. Nephrotic range proteinuria was observed in 17 (2.6%) and nonnephritic range proteinuria, in 239 (37.1%) recipients. The latter cohort was categorized into low-grade proteinuria (n = 224; 34.8%) and high-grade proteinuria (n = 15; 2.3%). Proteinuria at posttransplant 1 year highly correlated with serum creatinine values at posttransplant years 1 and 2 as well as estimated glomerular filtration rate but not creatinine clearance at postoperative year 2. A greater incidence of graft loss was observed among recipients with more severe proteinuria. Males, recipients with anti-hepatitis C virus antibody, unrelated donors, anti-thymocyte immunoglobulin at the time of reperfusion, maintenance immunosuppression with cyclosporine or without mycophenolate mofetil were strongly associated with the amount of proteinuria.

Conclusion

This study demonstrated the prevalence of proteinuria in kidney transplant recipient to be high. The presence as well as level of proteinuria were predictive markers for inferior allograft function.     

细胞因子基因多态性与移植肾慢性排斥反应的关系

目的探讨供、受者细胞因子基因多态性与移植肾慢性排斥反应的关系。方法用序列特异引物聚合酶链反应（PCR-SSP）方法，对144例肾移植受者和65例部分供者进行5种细胞因子[肿瘤坏死因子α（TNF-α）、白细胞介素6（IL-6）、白细胞介素10（IL-10）、转化生长因子β1（TGF-βt）、干扰素7（IFN-7）]基因型检测。结果TGF-β1。高分泌型的受者与中低分泌型受者相比，移植肾慢性排斥反应发生率明显升高，差异有统计学意义（P〈0．01）。TGF-β1高分泌型的供者与中低分泌型供者相比，移植肾慢性排斥反应发生率差异无统计学意义（P〉0．05）。TGF-β1，基因型为供者高分泌／受者高分泌组合时，移植肾慢性排斥反应发生率比所有其它基因型组合者高（P〈0．01）；而TGF-β1。基因型为供者中低分泌／受者中低分泌组合时，移植肾慢性排斥反应发生率比所有其它基因型组合者低（P〈0．01）。TNF-α、IL6、IL-10及IFN-γ的基因型与移植肾慢性排斥反应发生率的关系不明显。结论同时检测供、受者TGF-β1，基因多态性对预测移植肾慢性排斥反应发生率有指导意义。     

Outcomes of kidney allograft in recipients with kidney disease of unknown etiology

The etiology of renal disease is important because the primary renal pathology may affect the outcomes of kidney allograft with respect to recurrence, rejection, and survival. However, for a significant number of patients who undergo kidney transplantation, the disease etiology is unknown. Here, allograft outcomes for patients with kidney disease of unknown etiology (UEK) at three affiliated Korean hospitals were identified. The incidence of biopsy‐proven acute rejection (BPAR) for UEK was 22.9%, which was similar to the rates for diabetic nephropathy (DN, 24.4%) and IgA nephropathy (IgAN, 20.0%; p = 0.345). The cumulative incidence of post‐transplant glomerulonephritis (PTGN) among patients with UEK was significantly lower than that among patients with IgAN (p < 0.001). Overall graft survival of the UEK group was superior to that of the DN group (hazards ratio 0.39, 95% confidence interval 0.17–0.92, p = 0.030). Preemptive transplantation for UEK significantly reduced the incidence of BPAR (preemptive vs. non‐preemptive 9.6% vs. 30.3%, p = 0.001), but graft survival and recurrence were not affected by preemptive transplantation. The outcomes of kidney transplantation for patients with UEK were not inferior to those for patients with IgAN or DN. Preemptive kidney transplantation may be encouraged for UEK patients.     

Association studies of Toll-like receptor gene polymorphisms with allograft survival in renal transplant recipients of North India

Organ transplantation itself inevitably activates the innate immune system by Toll-like receptors (TLRs), potentially leading to allograft rejection and graft failure. We evaluated the possible association of TLR2, TLR3, and TLR9 polymorphisms of donor-recipient pairs and acute rejection in renal transplant patients of North India. TLR2 (-196 to -174 del), TLR3 (c.1377C/T; rs 3775290), and TLR9 (+2848 G/A; rs 352140) were genotyped using DNA samples from 200 donor-recipient pairs of live donor kidney transplantation by applying Restriction Fragment Length Polymorphism (RFLP) methodology. The variant allele frequency of TLR2 (-196 to -174 del) was significantly different between recipients and donors (7.5% vs. 5.0%; p = 0.049; OR = 3.9; 95% CI = 1.01-15.32). However, no significant association for allograft rejection was observed in transplant recipients for TLR3 and TLR9. Interestingly, a low prevalence of AA genotype of TLR9 + 2848 G>A was observed in rejecters when compared with non-rejecters, demonstrating protective association with allograft rejection (OR = 0.30, 95% CI = 0.12-0.88, p = 0.028). An allele in patients was also observed to be associated with higher rejection-free survival (log-rank = 0.044). These TLR gene polymorphisms, upon further evaluation, may be helpful in elucidation of immunobiological mechanisms associated with renal graft rejection.     

Multidrug resistance protein 2 genetic polymorphisms influence mycophenolic acid exposure in renal allograft recipients

BACKGROUND: Mycophenolic acid (MPA) is glucuronidated by uridine diphosphate-glucuronosyltransferases (UGTs) to its pharmacologically inactive 7-O-glucuronide metabolite (MPAG). MPAG is excreted into the bile via the multidrug resistance-associated protein 2 (MRP2/ABCC2), which is essential for enterohepatic (re)circulation (EHC) of MPA(G). METHODS: The objective of this study was to determine the relationship between single nucleotide polymorphisms (SNPs) in the MRP2 (G-1549A, G-1023A, A-1019G, C-24, G1249A, C3972T and G4544A) and UGT1A9 (C-2152T, T-275AandT98C) genes and MPA pharmacokinetics in 95 renal allograft recipients at days 7, 42, 90, and 360 after transplantation. In addition to mycophenolate mofetil, all patients received tacrolimus and corticosteroids as immunosuppression. RESULTS: At day seven after transplantation, in the absence of the MRP2 C-24T SNP, mild liver dysfunction was associated with significantly lower MPA dose-interval exposure and higher MPA oral clearance, while liver dysfunction did not affect MPA pharmacokinetics in patients with the MRP2 C-24T variant. A similar effect is noted for the C-3972T variant, which is in linkage disequilibrium with C-24T. At later time points after transplantation the MRP2 C-24T SNP was associated with significantly higher dose-corrected MPA trough levels. Patients with the MRP2 C-24T variant had significantly more diarrhea in the first year after transplantation. CONCLUSIONS: The MRP2 C-24T and C-3972T polymorphisms protect renal transplant recipients from a decrease in MPA exposure associated with mild liver dysfunction. Furthermore, this study suggests that the C-24T SNP is associated with a lower oral clearance of MPA in steady-state conditions.     

Association of cytokine polymorphisms with subclinical progressive chronic allograft nephropathy in Japanese renal transplant recipients: Preliminary study

BACKGROUND: The present study calculated the risk of developing subclinical progressive chronic/sclerosing allograft nephropathy (CAN) under tacrolimus-based immunosuppression according to genetic polymorphisms of cytokines and growth factors, and clinical events including delayed graft function (DGF), acute rejection (AR) and cytomegalovirus (CMV) infection. METHODS: The subjects were 50 recipients with stable graft function more than one year after renal transplantation. The criteria for subclinical progressive CAN were CAN grade 2 or 3 changes on Banff classification and stable serum creatinine (SCr) levels. Ten genetic polymorphisms were assessed. RESULTS: Eleven patients (22.0%) developed progressive CAN. The mean ages and SCr levels of recipients with and without progressive CAN were 41.2 and 47.1 years, and 1.46 and 1.22 mg/dL, respectively. There were no significant differences in donor age, number of HLA mismatches, DGF or CMV infection. Although the rate of AR episode seemed to be greater in patients with subclinical progressive CAN, the difference did not reach significance (P = 0.093). The frequencies of the interleukin (IL)-2 T-330G TT genotype (P = 0.046) and IL-4 C-590T C allele (P = 0.092) were higher in patients with progressive CAN. In univariate analysis, the presence of IL-2 T-330G TT (OR 4.57, P = 0.044) was associated with CAN development. CONCLUSION: The presence of IL-2 T-330G TT genotype may be a risk factor for CAN. Further studies with a large number of subjects and analyses of many cytokine polymorphisms would contribute to the ability to make prognostic determinations or tailor immunomodulatory regimens after renal transplantation.     

Natural cell-mediated cytotoxicity of kidney allograft recipients

Natural cell-mediated cytotoxicity (NCMC) displayed by peripheral blood mononuclear cells of kidney allograft recipients was examined against K562 cells to demonstrate the kinetics of NCMC activity in the posttransplant period. On 44 kidney allograft recipients 301 NCMC assays were performed between 1 and 84 months after transplantation. These patients were treated with the conventional immunosuppressive treatment consisting of steroid and azathioprine. NCMC activity sharply decreased after transplant surgery. A decreased NCMC activity continued during the first 6 months and the mean NCMC value was 19.2 +/- 14.1. In the second 30 months, NCMC activity also constantly decreased, almost to 10. It was lower than that of the first 6 months (P less than 0.01). After 37 months, some patients restored a normal NCMC activity and others showed a decreased NCMC activity. The mean value was 27.4 +/- 20.6 in the third 48 months. The depression of NCMC activity might be caused by the large dose of steroid and azathioprine in the first 6 months. In the third 48 months, NCMC activity might be dependent on the dosage of azathioprine alone. The activation of NCMC activity might be caused by acute rejection crisis.     

氯沙坦治疗肾移植后大量蛋白尿

目的 探讨氯沙坦对肾移植后大量蛋白尿的治疗作用.方法 接受尸体肾移植、术后时间达1年以上、24 h尿蛋白定量≥300 mg的患者82例,以计算器随机数法分为氯沙坦组和对照组,每组各41例.氯沙坦组患者连续服用氯沙坦达1年以上,剂量为50～100 mg/d;对照组患者连续服用氨氯地平达1年以上,剂量为5～10 mg/d.观察12个月,记录患者的血压、24 h尿蛋白定量、血肌酐等.结果 研究过程中,两组患者的血压均有所下降,但下降幅度的差异无统计学意义(P＞0.05).氯沙坦组研究开始时和研究结束时的24 h尿蛋白定量分别为(1.9±1.5)g和(1.1±0.8)g,二者的差异有统计学意义(P＜0.05),而对照组研究开始时和研究结束时24 h尿蛋白定量的差异无统计学意义(P＞0.05).与研究开始时相比较.氯沙坦组中血压控制者及血压未控制者的尿蛋白均有所减少,差异均有统计学意义(P＜0.05,P＜0.05).对照组中,仅血压控制者的尿蛋白较研究开始时有所减少(P＜0.05),血压未控制者的尿蛋白反而较研究开始时有所增加(P＜0.05).氯沙坦组和对照组中,治疗明显有效(尿蛋白下降≥50%)者分别占56.4%和15.8%,二者的差异有统计学意义(P＜0.01).结论 氯沙坦对肾移植后大量蛋白尿有一定的治疗作用,且该作用不依赖于患者血压的下降.